Evidence map›Paper›PMID 38898077›Full record

ArticleScientific reports2024

PLX038A, a long-acting SN-38, penetrates the blood-tumor-brain-barrier, accumulates and releases SN-38 in brain tumors to increase survival of tumor bearing mice.

Jinkyu Jung, Eric L Schneider, Wei Zhang, Hua Song, Meili Zhang, William Chou, Niranjan Meher, Henry F VanBrocklin, Mary Helen Barcellos-Hoff, Tomoko Ozawa and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Jinkyu Jung *Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Eric L Schneider *ProLynx, Inc, 135 Mississippi Street, San Francisco, CA, USA.
Wei ZhangNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Hua SongNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Meili ZhangNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
William ChouDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Niranjan MeherDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Henry F VanBrocklinDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Mary Helen Barcellos-HoffDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Tomoko OzawaBrain Tumor Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Mark R Gilbert *Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Daniel V Santi *ProLynx, Inc, 135 Mississippi Street, San Francisco, CA, USA. Daniel.V.Santi@prolynxinc.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Central nervous system tumors have resisted effective chemotherapy because most therapeutics do not penetrate the blood-tumor-brain-barrier. Nanomedicines between  ~ 10 and 100 nm accumulate in many solid tumors by the enhanced permeability and retention effect, but it is controversial whether the effect can be exploited for treatment of brain tumors. PLX038A is a long-acting prodrug of the topoisomerase 1 inhibitor SN-38. It is composed of a 15 nm 4-arm 40 kDa PEG tethered to four SN-38 moieties by linkers that slowly cleave to release the SN-38. The prodrug was remarkably effective at suppressing growth of intracranial breast cancer and glioblastoma (GBM), significantly increasing the life span of mice harboring them. We addressed the important issue of whether the prodrug releases SN-38 systemically and then penetrates the brain to exert anti-tumor effects, or whether it directly penetrates the blood-tumor-brain-barrier and releases the SN-38 cargo within the tumor. We argue that the amount of SN-38 formed systemically is insufficient to inhibit the tumors, and show by PET imaging that a close surrogate of the 40 kDa PEG carrier in PLX038A accumulates and is retained in the GBM. We conclude that the prodrug penetrates the blood-tumor-brain-barrier, accumulates in the tumor microenvironment and releases its SN-38 cargo from within. Based on our results, we pose the provocative question as to whether the 40 kDa nanomolecule PEG carrier might serve as a "Trojan horse" to carry other drugs past the blood-tumor-brain-barrier and release them into brain tumors.

Indexed as

Blood-Brain BarrierBrain NeoplasmsIrinotecanProdrugsAnimalsCamptothecinCell Line, TumorFemaleGlioblastomaHumansMiceXenograft Model Antitumor AssaysCamptothecinIrinotecanProdrugs

Identifiers

PMID38898077
PMCPMC11187204

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.